OBJECTIVEGene expression profiling of diffuse large B-cell lymphoma (DLBCL) of different immunophenotypes.

METHODSThe study included 156 cases of DLBCL, which were subclassified by immunohistochemistry including CD10, bcl-6 and MUM1. Affymetrix U133 plus2.0 oligonucleotide microarrays were used to obtain differential gene expression profiling of 9 DLBCL (3 representative cases from each immunophenotypical group) and 3 tonsils. Clinical stages of all 9 lymphomas were Ann Arbor stage IV.

RESULTSThe immunohistochemistry subclassified 156 cases of DLBCL into 3 groups: CD10(+) and/or bcl-6(+), MUM1(-) (group 1); CD10(+) and/or bcl-6(+), MUM1(+) (group 2); CD10(-) and bcl-6(-), MUM1(+) (group 3). By gene expression array, 9 lymphomas and 3 tonsils were clustered in an unsupervised fashion into 4 groups (A, B, C and D), which were in accordance with the immunophenotypical groups (group 1, 2, 3 and normal). A total of 81 genes were markedly decreased and 86 genes were over-expressed in all DLBCL groups. Although Group B lymphomas showed mixed immunophenotypical features of both germinal center B-cell-like DLBCL (Group A) and activated B-cell-like lymphomas (Group C), gene profile clustering showed that Group B was dissimilar to Group A or Group C, with 45 over-expressed and 27 uniquely expressed genes.

CONCLUSIONSGene expression profiling indicates that DLBCL can be subgrouped at the molecular level and can be identified by immunophenotyping. The gene expression profile of Group B lymphomas suggests that factors other than the cell-of-origin may contribute to the pathogenesis of DLBCL.